This application for an Asthma Clinical Research Network site presents the multitude of strengths which the University of Pittsburgh would bring to the ACRN. Asthma affects more than 14 million Americans, and disproportionately affects African-Americans and Hispanics. Guidelines for asthma management highlight the role of inhaled corticosteroids [ICS] for asthma, based on a large body of literature demonstrating superiority, on average, of ICS over other options, including leukotriene modifiers [LTM]. This recommendation is based on the concept that the majority of asthmatics will improve with ICS. A recent ACRN publication (MICE), however, strongly suggests that response to ICS is neither universal nor uniform. A principal theme of this application is that variability in response to therapy can be identified prospectively, and used to improve the care of patients with asthma. Genetic and metabolic factors underlie variability in clinical response. We propose to measure polymorphisms in genes related to asthma and in drug metabolizing enzymes, to measure functional activity of drug metabolizing enzymes, and to measure clinical response to ICS, LTM, and theophylline in the Determinants in Asthma of Response to Therapy [DART] protocol. We then may be able to use these factors as predictors of positive response to asthma therapy. Another key question is whether LTM, theophylline, or higher dose ICS improve asthma control, especially lung function and rates of exacerbation. This question will be addressed in the Evaluation of Supplemental Therapy for Asthma [ESTA] trial. The University of Pittsburgh offers an existing, productive infrastructure with a track record of productivity in clinical trials in asthma, and an NIH-funded basic and translational research program. We have a large existing cadre of asthma patients, links to the UPMC Health Plan for access to more than 5000 additional asthmatics, and a demonstrated history of recruiting and retaining minority subjects. We offer collaboration with the (Pitt) Center for Minority Health, extremely strong minority recruiting strategies, a strong GCRC, world-class gene expression microarray analysis, an innovative Center for Clinical Pharmacology, including a Clinical Pharmacology Analytic Facility, and a Pharmaco-genomics Core Laboratory. Pitt strongly supports collaborative, clinical network research. Data from the DART and ESTA trials can help to improve the care of patients with asthma.